Nonaqueous cold sterilant

ABSTRACT

A hypocompatible biodegradable nonaqueous cold chemical sterilant capable of killing a challenge of a wide range of target organisms including bacterial spores within ten minutes comprising a composition of interactive constituents including a monohydric alcohol, a polyhydric alcohol, a saturated dialdehyde and a cationic surface active agent in proportion by weight to reduce the surface tension of the bacterial spore wall, penetrate the bacterial spore wall and kill the nuclei of the bacterial spores and other target organisms without the need of removing residue.

This application is a continuation-in-part application of applicationSer. No. 642,709, filed Jan. 17, 1991, now U.S. Pat No. 5,145,663, thatis a continuation application Ser. No. 304,312, filed Jan. 31, 1989, nowabandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

A hypocompatible biodegradable non-aqueous cold sterilant effectiveagainst a wide range of pathogenic organisms including bacterial spores.

2. Description of the Prior Art

Sterilants are used in many areas, such as in the sterilization oflaboratory, surgical, dental and other equipment. It is customary inhospital practice to sterilize instruments overnight, using chemicalsterilizing agents or other sterilizing methods.

The most common methods of sterilization involve either the use ofpressurized steam, dry heat or ethylene oxide. However, some of thesemethods are cumbersome, tedious and time-consuming, often damage thesterilized material and require expensive equipment and skilledtechnicians.

Moreover, steam sterilization is impracticable for many plastic devicesand delicate instruments which are sensitive to elevated temperatures.

Many chemical sterilization methods have been developed as substitutesfor steam sterilization. Unfortunately most have shortcomings. Phenolsand formaldehyde compositions have considerable sporicidal activity buthave objectionable odors and extreme toxicity. Ethanol, isopropylalcohol and the quaternary ammonium compounds have been used, and thoughless odorous and toxic, lack the activity of the phenols andformaldehyde compositions.

Compositions comprising saturated dialdehydes with alkalinating agentshave also been used. Though such compounds are satisfactory as chemicalsterilization agents their sporicidal activity is limited to certain pHranges, require up to ten (10) hours to work, and have certain limits onstability.

U.S. Pat. No. 3,282,775 shows a sporicidal composition includingsaturated dialdehydes containing from 2 to 6 carbon atoms and a cationicsurface active agent. More specifically, these compounds includemalonaldehyde, succinaldehyde, oxaldehyde (glyoxal), adipaldehyde andpreferably, glutaraldehyde. The quantity of saturated dialdehyde usedmay vary from about 0.1 percent to about 2 percent depending upon whichparticular dialdehyde is selected. Moreover, one may safely depart fromthis concentration without seriously detracting from its effectiveness.For example, if desired, the final concentration of dialdehyde may beincreased up to as much as 10 percent or decreased as low as 0.05percent. However, amounts in excess of 2 percent are unnecessary,extremely toxic and wasteful. In actual practice a range of from 0.1percent to about 2 percent is preferred. The compounds may be dilutedeither with water or lower alkanols such as methanol, ethanol,isopropanol and the like, or with combinations to form aqueous-alcoholsolutions. The pH of the final solution may be either on the acid sideor the alkaline side and may be varied over a wide range of from about4.0 to about 9.0 though it is preferred to have the pH in the range offrom about 5.0 to 8.0.

U.S. Pat. No. 4,040,977 describes a preservative and disinfectingcomposition for aqueous emulsions, suspensions and solutions which areobtained by reaction in water of a haloacetamide or thiocyanoacetamideor mixture thereof; an alcohol or mixture of alcohols; and formaldehyde.

U.S. Pat. No. 3,697,222 describes a sterilization process achieved bycontacting a contaminated object with an aqueous acid glutaraldehydesolution at temperatures above about 45 degrees C. The sterilizingaction may be enhanced by ultrasonic energy. Sterilization also may beachieved using ultrasonic energy and aqueous alkaline glutaraldehydesolution.

U.S. Pat. No. 4,093,744 teaches a means for killing spores oninstruments and the like utilizing the combination of glutaraldehyde anda detergent selected from the group consisting of nonionic, anionic andampholytic surface active agents. The sporicidal kill activity ofglutaraldehyde is enhanced by the detergents.

U.S. Pat. No. 4,048,336 relates to a means for killing spores oninstruments and the like utilizing the combination of 18 glutaraldehydeand a monoaldehyde, such as, for example, formaldehyde. The sporicidalkill activity of the composition is more rapid than previously possibleand more effective than the use of either glutaraldehyde or monoaldehydealone. Unfortunately, this composition is far more toxic than withoutglutaraldehyde.

U.S. Pat. No. 4,208,404 shows an aqueous solution of glutaraldehyde ofacid pH value with dissolved quantities of certain highly ionized saltsto kill dormant spores at room temperature.

U.S. Pat. No. 4,294,797 describes a composition to sterilize medicalinstruments comprising an alcohol-aldehyde active substance combinationin a proportion of 5 to 15 percent by weight. The preferred alcohol isisopropanol and the preferred aldehyde is formaldehyde or a succinicacid dialdehyde complex and the preferred ratio of alcohol to aldehydeis 1:1.

U.S. Pat. No.2,889,243 shows a chemical composition having antiviralactivity comprising hydroxpyruvaldehyde ether.

U.S. Pat. No. 4,173,653 teaches an Oxydiacetaldehyde is used as anactive antimicrobial agent in an aqueous solution for disinfecting orsterilizing. The activity against bacteria or spores can be improved byadding alkalinating agents or alcohols such as isopropanol, or byraising pH or by raising the temperature.

U.S. Pat. No. 4,923,899 describes an aqueous composition for killingbacteria, spores, fungi and viruses on nonabsorbent surfaces comprisingat least one quaternary ammonium salt, at least one aliphatic dialdehydehaving from two to six carbon atoms, and at least one aliphatic hydroxylcompound having from one to eight atoms. Optionally, a chelating agentand an inorganic nitrite salt may be employed. This sterilant killsbacteria, spores, fungi and viruses over a pH range from about pH 4 toabout pH 9.

U.S. Pat. No. 3,968,250 describes a method for disinfecting orsterilizing medical, surgical, dental instruments or other objects inliquid phase with improved sporicidal compositions by combining nonionicand anionic surfactants with aqueous or alcoholic glutaraldehydesolutions. The method can be used also with ultrasonic irradiation overa wide frequency range of from 10 to 850 kHz.

U.S. Pat. No. 3,968,248 and U.S. Pat. No. 3,912,450 teach similarmethods.

U.S. Pat. No. 4,103,001 shows a room temperature aqueous sterilizingcomposition comprising from 0.75 percent by weight of glutaraldehyde andfrom 4-15 percent by weight of phenol and a metal phenate, preferablysodium phenate. Optionally present are 1-5 percent by weight of sodiumtetraborate, 2-10 percent by weight of a humectant such as glycerol,di-ethylene glycol or propylene glycol and a surfactant. A preferred pHrange is pH 7.0-7.4.

U.S. Pat. No. 4,004,024 describes a method for controlling bacteria,fungi and spores which comprises applying thereto a bacterially,fungicidally and sporicidally effective amount of a furan selected from2-(R₁ O)-5-(R₂₀ O)-2,5-dihydrofuran and 2-(R₁ O)-5-(R₂ O)-tetrahydrofuran or mixtures thereof; a process for preparing a2,5-bis(-R₁ O)-2.5-tetrahydrofuran and 2.5-bis((R₁ O)-tetrahydrofuranand 2.5-bis(benzyloxy)-tetrahydrofuran.

U.S. Pat. No. 4,436,754 describes a disinfecting and sterilizingcomposition comprising an aqueous solution containing a 2 to 6 carbonatom dialdehyde and may also contain formaldehyde and a diol ormonosubstituted diol of the formula RO(CH₂ YCH₂ O)_(n) CH₂ CH₂ OH; whereR is H or CH₃ and n is an integer from 1 to about 22 with a wide rangeof pH from pH 2 to pH 9.

U.S. Pat. No. 4,937,072 a sporicide having a defined period ofsporicidal activity comprising three components including a peroxide orperoxide generating material, a peroxidase and a salt of iodine whichserves as a donor molecule, storing the three components in anonreacting state to maintain the sporocide in an inactive state andadmixing the three components in an aqueous based carrier to cause acatalyzed reaction by said peroxidase for generating free radicalsand/or by-products from the iodide salt (donor molecule) and contactingthe surface or object to be sterilized with the activated mixture. Theconcentration level of the three components can be selected such that anactive sporocidal state is maintained for any desired period of time.

U.S. Pat. No. 4,122,192 describes a solid composition for producing adisinfectant or sterilant comprising a disinfecting or sterilizingamount of saturated dialdehyde having from 2 to 6 carbon atoms absorbedon an inorganic or organic particulate carrier material and, in somecases, an alkalinating agent.

U.S. Pat. No. 3,983,252 describes a disinfectant composition comprisinga dialdehyde and an alkali metal salt of a hydrocarbon carboxylic acidin aqueous solution and, optionally, an alcohol and/or a diol and/or atriol, and are as potent as, but substantially more stable than, knowndialdehyde containing disinfectant compositions.

U.S. Pat. No. 3,653,499 describes a germicidal, sporicidal and detergentcomposition which prevents coagulated blood from adhering to instrumentsduring sterilization and used to decontaminate surgical items, such asneedles and sponges comprising paraformaldehyde having an averagemolecular weight of about 360 free from polymer chains over a molecularweight of 3,000, alkali metal tripolyphosphate and a water solublebuffer, such as sodium carbonate, to give a final aqueous solutionhaving a pH between about 10 and 11. If the materials are substantiallyanhydrous, the constituents can be mixed together in a powder and storedin a container hermetically sealed against the entrance of moisture. Ifthe constituents or any of them are not substantially anhydrous, thecomposition must be in a two-part package separately sealed inwaterproof pouches, one containing the paraformaldehyde and the otherthe polyphosphate and buffer.

U.S. Pat. No. 4,978,530 describes a process for sanitizing, disinfectingand killing spores involving providing a tangible object made frompolymeric material impregnated with an aqueous glutaraldehyde solutionpackaged in an air-tight enclosure, removing the impregnated tangibleobject from the enclosure and applying the impregnated tangible objectto the surface to be sterilized and/or sanitized and disinfected so asto expose spores, bacteria, virus and other microorganisms present onthe surface to the action of the glutaraldehyde solution. A sanitaryattachment for a receiver or mouthpiece of a telephone made from plasticmaterial incorporating a glutaraldehyde solution. A fabric made fromcellulosic or plastic material having sporicidal and/or sanitizing anddisinfectant activity as a result of being impregnated with aglutaraldehyde solution. A method for sanitizing and disinfecting and/orrendering fabric sporicidal involves impregnating a fabric with anaqueous glutaraldehyde solution prior to packaging the fabric in anair-impervious container until ready for use.

Various spray germicides for sanitizing such surfaces is typified byU.S. Pat. No. 3,445,564. U.S. Pat. No. 3,445,564 is directed to amethod, compositions and articles for sanitizing public or communalfacilities prior to individual use. The method consists of applying athin layer of a rapidly drying liquid germicidal composition to asurface such as a toilet seat. The rapidly drying germicidalcompositions consist essentially of a lower aliphatic alcohol and atleast about 5 percent of a volatizing agent such as acetone. Isopropylalcohol has excellent germicidal activity and is sufficiently volatileto give a satisfactory drying rate when blended with suitableproportions of a volatizing agent. Inasmuch as the lower aliphaticalcohols are not sufficiently volatile to afford usefully short dryingtimes for practical purposes in the method and articles of the Kirschnerinvention it was necessary to include a volatizing agent in thegermicidal composition. The proportion of volatizing agent to loweraliphatic alcohol in the rapidly drying germicidal compositions employedin the invention may vary widely depending upon a number of factors,which include among others, the volatility of the alcohol employed, thevolatility of the volatilizing agent, the desired drying rate of thegermicidal composition, the amount of germicidal agent applied to thesurface to be treated and the method of application of the germicide,not to mention the prevailing conditions of temperature and relativehumidity under which the product is to be employed.

Although the isopropyl alcohol-acetone composition of U.S. Pat. No.3,445,564 has germicidal activity against bacteria, fungi and otherlower organisms, additional antibacterial, antifungal or other activeingredients may be incorporated to enhance the overall germicidaleffectiveness. Suitable germicidal additives include the well knownantibacterial quaternary ammonium compound. In essence, U.S. Pat. No.3,445,564 teaches the use of isopropyl alcohol to kill a limited numberof germs on a dry toilet seat with the addition of acetone to volatizean already highly volatile chemical to rapidly dry the toilet seat foruse within 30 seconds.

The use of a dye in a bactericidal solution as disclosed in U.S. Pat.No. 2,449,274 is employed to provide a visual indication of theeffectiveness of such sprays.

U.S. Pat. No. 4,678,658 shows an aerosol spray for use in disinfecting asurface for personal use such as a public restroom facility ortelephone. The composition and delivery of the compositions provides forthe placement of a spray of disinfectant which includes a dye thatdisappears as the spray effects the germicidal activity of thedisinfectant. The composition is also rapidly drying, so that the dyedisappears as well as the disinfecting composition leaving the surfacedry. However, the spray is corrosive and environmentally unsafe.

U.S. Pat. No. 3,821,413 discloses a formulation of materials whichpermits an effective, uniform rate of evaporation of glycols from an aircirculator device to reduce airborne bacteria in the surroundingatmosphere. It was observed that the relative amounts and identities ofthe components of the invention are critical to the attainment of thedesired continuous evaporation of glycols over a prolonged period oftime.

The composition of U.S. Pat. No. 3,821,413 is a single phase liquidcomposition especially adapted for volatilization at a substantiallyuniform rate from the air circulator device. Generally speaking, thecomposition includes three essential components (1) a glycol, (2) anorganic polar coupling compound for maintaining the homogeneity preventsthe glycol from separating from the mixture during evaporation of themixture into the atmosphere and (3) an organic, relatively non-polarcompound for forming hydrophobic micelles with the glycol molecules inthe resulting mixture for reducing the affinity of the glycol toatmospheric moisture and thereby increasing the rate at which the glycolmay be evaporated into the atmosphere.

The composition contains the glycol germicide. If desired, othersuitable germicides or antiseptic agents can be added provided, however,that the glycol concentration of the composition does not fall below 5percent by weight of the total mixture. Such germicides includequaternary ammonium compounds, phenols, bisphenols, salicylanilides,carbanilides, formaldehyde and chloride.

The required glycol evaporation rate for attaining the desired airsanitizing performance depends on the satisfactory stability and uniformnature of the liquid composition during evaporation from the mixture.Accordingly, the compositions of the invention include from about 2percent to about 40 percent by weight of an organic polar couplingcompound for maintaining the homogeneity of the mixture to prevent theglycol from separating from the mixture during the evaporation process.

The affinity of glycols to attract atmospheric moisture significantlyreduces their volatility and impairs their evaporation rate.Accordingly, the compositions of the invention include from about 5percent to about 80 percent by weight of an organic, relativelynon-polar compound for forming hydrophobic micelles surrounding theglycol molecules in the mixture for reducing the affinity of the glycolto atmospheric moisture and thereby increase the rate of evaporation ofthe glycol. Without this micelle formation, it was found that the glycolor mixture of glycols in the mixture cannot evaporate appreciably in anair circulator device containing a wick immersed in the liquidcomposition.

U.S. Pat. No. 3,806,593 is directed to an acne treatment medicationapplied to the skin for preventing the formation of acne or decreasingalready established ache. An important factor for the occurrence of acheis the presence of bacteria in the sebaceous glands in the skin. It isknown that the bacteria in the sebaceous glands form esterases whichhydrolyze the sebum fats to alcohols and free fatty acids.

The medicinal ache-preventing or ache-diminishing composition of U.S.Pat. No. 3,806,593 is based on the bacterial esterase activity in thesebaceous glands which together with the water already present in theskin can hydrolyze an ester having a good penetration capacity into thesebaceous glands to form one and preferably two antibacterially activecomponents, viz. an acid and an alcohol, which are harmless to the skin.The active compound in the composition is one or more esters chosen fromthe group consisting of ethyl lactate, isopropyl lactate and/or glycerolmono or dilactate. The esters hydrolyze in the sebaceous glands due tothe esterases present in the glands to form the corresponding acids andalcohols. Lactic acid and the lower alcohols and also glycerol to acertain extent exert a good antibacterial activity when formed in situin the sebaceous glands. The esters are lipophilic and can thuspenetrate into the said glands. Even if a beneficial action can beachieved by application of the ester or esters per se, it, has beenfound to be suitable to apply the ester in the form of a solution inethyl alcohol or isopropyl alcohol. The alcohol prevents hydrolysis ofthe ester already in the composition, the alcohol moves the hydrolysisequilibrium towards ester formation. The alcohol can also facilitate thepenetration of the ester into the skin.

As is well-known alcohol in high concentrations may cause a drying-outof the skin. To counteract this effect, the composition may include amoisture-retaining agent such as a lower, suitably water-free polyol,viz. propylene glycol or glycerol. The content of propylene glycol orglycerol in the composition according to the invention may be up to 25percent, suitably not more than 10 percent by weight and preferably 1-5percent. High levels of polyol tend to make the composition smeary uponapplication on the skin and should thus be avoided.

The preferred composition according to the invention consists of about15 percent by weight of ethyl lactate, about 2 percent by weight ofpropylene glycol, the remainder being ethyl alcohol.

In summary, U.S. Pat. No. 3,806,593 relates to acne medicationcomprising esters that hydrolize in the sebaceous glands in combinationwith an alcohol to prevent hydrolysis of the esters as well as tofacilitate the penetration of the ester into the skin, and propyleneglycol or glycerol to prevent drying of the skin. The preferred ratio ofthe constituents is 15 percent to 83 percent to 2 percent respectively.

U.S. Pat. No. 4,664,909 discloses a stable, fast drying pituitous powderdeodorant suspension in an alcohol media containing a minimal amount ofwater and a critical amount of the essential hydroxyethyl cellulose asthe suspending agent.

The fast drying pituitous suspension of particulate material in anaqueous alcohol media contains hydroxyethyl cellulose at levels aboveits normal solubility limit by the polyhydric alcohol.

More specifically, U.S. Pat. No. 4,664,909 relates to stable pituitoussuspensions of particulate material, preferably about 1-20 percent,uniformly suspended in alcohol/aqueous media containing a high alcoholcontent and a lower water content. The alcohol media may be a lowermonohydric alcohol selected from the group consisting of methanol,ethanol, isopropanol and mixtures thereof. The use of polyhydricalcohols such as propylene glycol, butylene glycol and polyols thereof,and glycerin decreases the critical water level required in thehydroxyethyl cellulose-containing alcohol media.

It has been unexpectedly found that powders can be suspended inalcoholic/aqueous media containing a high alcohol content and a lowerwater content by using the water soluble polymer hydroxyethyl celluloseat critical levels above its ethanol solubility range which may bebroadened by specified polyhydric alcohols. This polymer is unique inits property to form stable suspensions.

Specifically, polyhydric alcohols can be partially substituted for themonohydric alcohol, not to exceed the monohydric alcohol content. Themonohydric alcohol content, such as ethanol, must exceed the uppersolubility level for the water soluble polymer hydroxyethyl cellulose inethanol or other lower alkanol. The reported upper solubility level ofthis water soluble polymer in ethanol is 70 percent. Below this leveland within normal soluble use ranges, a uniformly viscous liquid isobtained which pours evenly. Although, it appears aestheticallydesirable, it will not support suspended powder and segregation occurs.However, at ethanol concentrations above its solubility range, thepolymer becomes less soluble and forms the desired pititious typeliquid. If ethanol is further increased resulting in very low waterlevels the polymer will precipitate out and its suspending propertiesare again lost. Accordingly, a 70:30 ratio of ethanol-water is optimum.However, it was found that this problem can be eliminated by thesufficient addition of a polyhydric alcohol such as glycerin, propyleneglycol, butylene glycol and polyglycols thereto.

Accordingly, it has been found that the monohydric alcohol constitutesabout 55-85 percent; and the water content may be as low as 5 percent ifat least 10 percent polyhydric alcohol is also present in thesuspension. The combined water and polyhydric alcohol content is atleast 15 percent and may be up to about 25 percent. Thus, it is apparentthat the proportions of monohydric alcohol, water and polyhydric alcoholare interdependent.

In summary, U.S. Pat. No. 4,664,909 teaches a fast-drying deodorantcomprising a critical amount of hydroxyethyl cellose as the deodorant toencapsulate or isolate bacteria to prevent growth of the bacteria,suspended in a solution of monohydric alcohol to provide the fast dryingcharacteristics and polyhydric alcohol to improve the overall solubilityof the solution to allow the use of increased levels of monohydricalcohol. The relative proportions of the monohydric alcohol, water andpolyhydric alcohol are driven or determined by the desired solubilityand therefore are interdependent.

U.S. Pat. No. 3,966,902 disclosed various polymer complex carriers suchas propylene glycol for use with an active ingredient such as adisinfectant or fragrance.

U.S. Pat. No. 4,690,779 refers to the use of propylene glycol incombination with alcohol and fragrances. This composition is both toxicand non-biodegradable.

U.S. Pat. No. 4,209,500 teaches a composition suitable for use inaerosol sprays including an anhydrous alcohol and fragrance or perfume.This composition is corrosive, non-biodegradable and non-evaporative.

U.S. Pat. No. 4,689,168 describes a hard surface cleaning compositionsuitable for glass, chrome, plastic, enamel and other hard surfaces. Thecomposition is applied to the hard surface as an emulsion of an aqueousphase and an oil phase. The bubbling action is caused by the evaporationof volatile constituents from the film or layer of applied compositions,as well as the desire for the aqueous and oil phase components toreform. The bubbling action, characterized by small bubbles of volatilecomponents erupting from the surface of the composition film aids inlifting soil from the hard surface. As an apparent consequence, the rateof cleaning is accelerated. The composition comprises a polar organicsolvent or mixture of solvents, a nonvolatile surfactant, a volatilesurfactant such asn an acetylenic alcohol or diol, a volatileorganosiloxane oligomer and water.

U.S. Pat. No. 4,983,317 teaches a liquid composition for cleaning a widevariety of hard surfaces, particularly metallic, plastic, tile,porcelain, glass and mirrored surfaces comprising a polyacrylic acid ora polyacrylate resin builder in combination with a hydrotrope which isan alkali metal salt of a C₂₁ dicarboxylic acid. The organic solvent maybe selected from the group consisting of alkylene and polyalkyleneglycols of from 2 to 6 carbon atoms and lower alkyl ethers of alkyleneand polyalkylene glycols of from 3 to 8 carbon atoms, the alkyl etherhaving from 1 to 4 carbon atoms. A lower aliphatic alcohol of from 2 to4 carbon atoms may also be included in the composition to adjustevaporation rate of the composition.

U.S. Pat. No. 5,064,635 describes a mixture of one or more surfactants(detergents) with the pH sensitive dye. The surfactant can be dilutedwith water to give the desired cleaning strength. The surfactant can bean anionic, nonionic, amphoteric or mixtures of the three types. Typicalanionic surfactants used are petroleum sulfonates, such as sodiumdodecylbenzene sulfonate, alcohol sulfates such as sodium lauryl sulfateand ethoxylated higher fatty alcohol sulfates such as sodium laurylether sulfate. Typical nonionic surfactants are primary alcoholethoxylates, secondary alcohol ethoxylates, alkyl phenol ethoxylates andalkanolamides. The amphoteric surfactants include a number of types ofcarboxylates derived from fatty imidazolines such as sodiumdicarboxyethylcoco phosphoethyl imidazoline or fatty proprionates suchas cocoamphoproprionate or cocoamphodipropionate. The composition of abasic cleaner includes the surfactant or mixture of surfactants at about0.1 percent to about 20.0 percentage by weight. This range of surfactantis for usage in a nondiluted product for household use. Thymolphthaleinin the range of about 0.01 percent to about 1 percent by weight willgive a broad range of blue color when varying intensity using an alkalisystem to adjust the pH of the composition.

U.S. Pat. No. 4,965,063 and U.S. Pat. No. 5,057,303 teach compositionssimilar to U.S. Pat. No. 5,064,635.

U.S. Pat. No. 4,329,334 shows a homogeneous liquid anionic-amphotericbased antimicrobial conditioning shampoo which includes about 0.5 to 2.5percent of the antimicrobial agent, 1-imidazolyl-1-(4-chlorophenoxy)-3,3-dimethylbutan-2, one, solubilized in an aqueous solution of criticalamounts of a mixture of the following specific ingredients: about 10-40percent by weight of an anionic sulfate or sulfonate surface activeagent; about 0.1-7.5 percent by weight of an amphoteric surfactantselected from the group consisting of cocobetaine, cocosulfobetaine,cocoamidopropylbetaine, cocoamidopropylsulfobetaine or combinationsthereof; a nonionic surface active agent selected from the groupconsisting of a tertiary amine oxide, a polyoxyethylene hexitanmono-higher fatty acid ester and mixtures thereof; and about 0.5-2percent by weight of a lower aliphatic monohydric or polyhydric alcoholor mixtures thereof in certain critical amounts to avoid precipitationof the antimicrobial agent.

U.S. Pat. No. 3,654,165 teaches a cleaner-sanitizer for use on telephoneinstruments including a fast-acting, penetrative, quick-dryingbacteriocidal detergent solution which leaves a safe, active residue ofselected proportions of sodium lauryl sulfate, dimethyl sulfone,isopropanol and iodine in solution.

U.S. Pat. No. 4,793,988 describes a composition for disinfecting asurface, such as a public restroom facility or telephone. Thecomposition and delivery of the composition provides for the placementof a thin layer of disinfectant including a dye. The dye disappears asthe thin layer effects the germicidal activity of the disinfectant. Asample of the germicidal composition was prepared with 400 mg of sodiumdodecyl sulfate (SDS), 400 mg of octyl phenoxy polyethoxyethanolmarketed as Triton X-100 and 100 mg of blue dye thymophthalein. Thiscomposition was tested for germicide effectiveness against Herpessimplex virus type 2, Neisseria gonorrhoeae, Staphylococcus aureus,Escherichia coli 011K58, Shingela sonnei, Salmonella typhimurium andCandida albicans.

U.S. Pat. No. 4,975,217 describes germicidal compositions for directapplication to human skin including an organic acid, e.g., malic acid,and an anionic surfactant, e.g., a sodium alpha-olefin sulfonate, asactive ingredients, and can optionally include an alcohol, e.g.,specially denatured ethyl alcohol, as an additional active ingredient.When formulated as soaps and lotions, the compositions have been foundto produce more than a 2.0 log reduction in bacteria applied to skin.Organic acids and anionic surfactants, e.g., malic acid and a sodiumalpha-olefin sulfonate surfactant, are used as active ingredients ingermicidal products which are applied directly to the skin, such ashand-washing soaps, skin-care lotions, soapy-lotions, or wipescontaining these materials. Optionally, the products can include analcohol, such as, specially denatured ethyl alcohol, ethyl alcohol andisopropyl alcohol as an additional active ingredient. Theseformulations, in addition to killing viruses, also effectively killbacteria and yeasts. In particular, the formulations have been found tokill a variety of microorganisms in both in vitro experiments performedin test tubes and, even more importantly, in in vivo experimentsperformed on human hands. Moreover, notwithstanding their germicidalactivity, the formulations have been found to be non-irritating to humanskin.

U.S. Pat. No. 4,046,706 shows a composition for cleaning contact lensescomprising a poly(oxyethylene)-poly(oxypropylene) block copolymer havinga molecular weight between 1900 and 15,500, a water solubility in excessof about 10 gms per 100 nl, a cloud point in 1 percent aqueous solutionsabove about 30 degrees C., and a foam height in excess of 30 mm; amicrobial growth inhibitor; ethyl or isopropyl alcohol; an amphotericsurfactant and water.

U.S. Pat. No. 3,578,499 teaches a powder composition containing agelling agent, a neutral diluent, a wetting agent and a dye or coloringadditive. The powder gelling composition when added to water forms agel. Acid or alkaline materials are added for cleaning, biocidal agentsfor sanitizing or other materials to produce a desired effect. Thesignificant advantage of this method is the increased residence time andhence contact time between agents in the gel and the surface to be actedon. A third component included in the gelling composition is a wettingagent exemplified by a linear alkyl benzene sulfonate type materialwherein the alkyl group may include from about 12 to 14 carbon atoms.The wetting agent should be desirably characterized as a anionic agentalthough it is recognized that nonionic surfactants may also beemployed. One wetting agent found useful herein is the commerciallyavailable sulfonate of dodecylbenzene.

U.S. Pat. No. 2,333,124 describes a method for sterilizing air ladenwith bacteria or other pathogenic organisms comprising contacting theair with a mixture of glycols in vapor form in proportions to provideabout 1 gram of such glycols in vapor form to not more than about 5 to 7million cubic centimeters of air.

U.S. Pat. No. 2,857,315 shows a stable anti-perspirant stick having abase comprising a sodium stearate-propylene glycol soap gel having anactive anti-perspirant agent sodium zirconium lactate. The sodiumstearate-propylene glycol soap gel may contain alcohol in an amount notsubstantially greater than the propylene glycol by weight.

Additional examples of the prior art are found in U.S. Pat. No. 580,213;U.S. Pat. No. 3,282,776; U.S. Pat. No. 4,201,764; U.S. Pat. No.4,282,179; U.S. Pat. No. 4,265,899; U.S. Pat. No. 4,283,421; U.S. Pat.No. 4,364,515; U.S. Pat. No. 4,550,105, U.S. Pat. No. 4,105,431; U.S.Pat. No. 4,243,403; U.S. Pat. No. 4,278,206; U.S. Pat. No. 4,322,475;U.S. Pat. No. 4,436,732; U.S. Pat. No. 4,464,293; U.S. Pat. No.4,597,887, U.S. Pat. No. 4,252,694; U.S. Pat. No. 4,279,762; U.S. Pat.No. 4,325,201; U.S. Pat. No. 4,540,505; U.S. Pat. No. 4,675,397 and U.S.Pat. No. 4,915,934.

Examination of the prior art reveals most existing compositionsavailable are either toxic or non-biodegradable or both. Toxic chemicalsthat are not biodegradable contaminate our environment, the soil and thewater supply.

In recognition of the dangers of existing disinfectants, healthfacilities are required to notify employees that toxic chemicals are inuse and advise them of the possible hazards that result or could resultas a consequence of misuse or a spills. Such notices must also be givento the community at large.

Other laws and regulations require users to document the use of toxicchemicals and require that the excess, the waste, or the residue becollected and properly stored. These materials must be collected bylicensed and approved toxic waste companies, taken to an authorizeddisposal site and legally destroyed. The cost of disposing of such toxicmaterial is often more expensive than the initial purchase price.

Sterilants today should be non-toxic or low in toxicity andbiodegradable and capable of killing bacterial spores quickly andeffectively. Further, such disinfectants and sterilants should bechemically compatible with the numerous aparatus and instruments foundin modern healthcare facilities.

As described more fully hereinafter the instant invention is directed toan environmentally safe composition capable of killing anaerobic andaerobic bacteria, viruses including the HIV virus, mildew, mold, fungusand bacterial spores. The principal complementary sporicidal ingredientsof the invention are selected from a group of monohydric alcohols, agroup of polyhydric alcohols, a group of saturated dialdehydes and agroup of cationic surface active agents.

In the past such alcohols have had limited use outside the laboratorydue to various undesirable characteristics of alcohol. For example, ithas been universally accepted that alcohol has very limited applicationas a widely used disinfectant because alcohol is unable to penetrateprotein rich material, evaporates quickly, has limited stability andshelf life, has a pungent odor and tends to form a glaze on hardsurfaces possibly hiding or covering visible contamination.

The instant invention has evolved from an extensive development programinvolving the unexpected formulation of certain chemicals to reduce orinhibit those undesirable features of alcohol and to make alcohol safeand effective for use outside the laboratory.

SUMMARY OF THE INVENTION

The present invention relates to a hypocompatible biodegradablenonaqueous cold chemical sterilant for use in manual bucket systems aswell as automated sterilizer systems to kill a wide range of pathogenicorganisms including bacterial spores.

The cold chemical sterilant comprises a composition including amonohydric alcohol, a polyhydric alcohol, a saturated dialdehyde and acationic surface active agent.

The monohydric alcohol is selected from the group consisting ofisopropyl, methyl, ethyl, n-propyl, n-butyl, tert-butyl alcohol andallyl alcohol and mixtures thereof. The polyhydric alcohol is selectedfrom the group consisting of propylene glycol; 1,3 propanediol; 1,2butanediol, polyethylene glycol with molecular weight of less than 800;glycerol and 1,4 butanediol and mixtures thereof.

The saturated dialdehyde is selected from the group consisting ofmalonaldehyde, succinaldehyde, oxaldehyde (glyoxal), adipaldehyde andglutaraldehyde. The cationic surface active agent is selected from thegroup consisting of cetylpyridinium chloride, methylbenzethoniumchloride, dodecylamine, hexadecylamine, hexadecylamine hydrochloride,dodecyl aniline, oleyl methylamine ethylene diethylamine methyl sulfate,oleyl benzylamino ethylene diethylamine hydrochloride, sulfate of laurylpyridinium, octadecyl methylene pyridinium acetate, methyl sulfate ofdimethyloctadecyl sulfonium, betaine of diethyl aminoacetic acid,cetylpyridinium bromide, dodecyltrimethylammonium bromide,hexadecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide,benzalkonium chloride, benzethonium chloride,benzyldimethyldodecylammonium bromide, benzyldimethyl- hexadecylammoniumchloride, benzyldimethyltetradecylammonium chloride,benzyltrimethylammonium methoxide, cetyldimethylethylammonium bromide,decamethonium bromide, dimethyldioctadecylammonium bromide,methylbenzethonium chloride, methyl mixed trialkylammonium chloride,methyltrioctylammonium chloride, 4-picoline dodecyl sulfate,n,n,n'poloxyethylene (10)-n-tallow-1,3-diamino propane and octadecylchloromethyl ether.

The relative proportions by weight of each of the four constituentscompliment each other to reduce the surface tension of the bacterialspore wall, penetrate the bacterial spore wall and kill the nuclei ofthe bacterial spores and other target organisms without the need ofremoving residue.

The hypocompatible biodegradable nonaqueous cold chemical sterilant inliquid form may be used in manual bucket systems or automatic sterilizersystems. Alternate systems may include a towelette or an absorbent wipecontaining the product in an airtight enveloping material such as sealedfoil or other wrapping material could be used for a single application.

The invention accordingly comprises the features of construction,combination of elements, and arrangement of parts which will beexemplified in the construction hereinafter set forth, and the scope ofthe invention will be indicated in the claims.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Various sterilizing compositions and delivery devices have beendeveloped to kill various pathogenic organisms including bacterialspores. The wide range of application or use is limited by the chemicaland biological effect of such compositions on the various surfaces anddelivery means exposed to such compositions.

The present invention relates to a hypocompatible organic or nonaqueouscold chemical sterilant for application on medical instruments, andother devices which is effective against a wide range of targetorganisms including bacterial spores.

The cold chemical sterilant comprises a hypocompatible biodegradablenonaqueous or organic composition including a monohydric alcohol,polyhydric alcohol, saturated dialdehyde and a cationic surface activeagent combined in relative proportions by weight to sterilize medicaland dental instruments and other devices such as scopes and dentalhandpieces. The application of the cold chemical sterilant is capable ofkilling a challenge of the pathogenic or target organisms discussedherein within ten minutes and without leaving an unacceptable residue.

The monohydric alcohol is selected from the group consisting ofisopropyl, methyl, ethyl, n-propyl, n-butyl, tert-butyl and allyl andmixtures thereof. The preferred monohydric alcohol is isopropyl.

The polyhydric alcohol is selected from the group consisting ofpropylene glycol; 1,3 propanediol; 1,2 butanediol, polyethylene glycol,glycerol and 1,4 butanediol and mixtures thereof. The preferredpolyhydric alcohol is polyethylene glycol with a molecular weight of 400or less. The polyethylene glycols suitable for use are well known andcommercially available. Polyethylene glycols, which are designated by anumber that represents the average molecular weight, range from clearviscous liquids at room temperature, PEGs 200, 300, 400 and 600, to softsolids PEGs, 1000 and 1450, to waxy solids available in the form offlakes or powders, PEGs 3350, 8000 and 14000.

The saturated dialdehyde is selected from the group consisting ofmalonaldehyde, succinaldehyde, oxaldehyde (glyoxal), adipaldehyde andpreferably, glutaraldehyde.

The cationic surface active agent is selected from the group consistingof methylbenzethonium, dodecylamine, hexadecylamine, hexadecylaminehydrochloride, dodecyl aniline, oleyl methylamine ethylene diethylaminemethyl sulfate, oleyl benzylamino ethylene diethyamine hydrochloride,sulfate of lauryl pyridinium, octadecyl methylene pyridinium acetate,methyl sulfate of dimethyloctadecyl sulfonium, betaine compound ofdiethyl aminoacetic acid, octadecyl chloromethyl ether, cetylpyridiniumbromide, dodecyltrimethylammonium bromide, hexadecyltrimethylammoniumbromide, tetradecyltrimethylammonium bromide, benzalkonium chloride,benzethonium chloride, benzyldimethyldodecylammonium bromide,benzyldimethylhexadecylammonium chloride,benzyldimethyltetradecylammonium chloride, benzyltrimethylammoniummethoxide, cetyldimethylethylammonium bromide, decamethonium bromide,dimethyldioctadecylammonium bromide, methylbenzethonium chloride, methylmixed trialkylammonium chloride, methyltrioctylammonium chloride,4-picoline dodecyl sulfate, n,n,n'poloxyethylene(10)-n-tallow-1,3-diamino propane and preferably cetylpyridiniumchloride.

As used herein, target organisms refers to pathogenic organismsincluding Staphylococcus areus, Pseudomonas aeruginosa and Salmonellacoleraesuis and viruses including HIV, tuberculosis, polio and herpessimples 2 as well as the fungus Trichophyton mentagrophytus, mold,mildew and bacterial spores including Bacillus subtilis, andColostridium sporogenes.

As used herein, the term non-toxic refers to the acute dermal, acuteinhalation and acute oral dosage as defined in 40 Code of FederalRegulations, Section 152.3.

As used herein, the term biodegradable refers to decomposition in thepresence of 25 percent organic material within 90 days at 69 degrees F.(Standard Temperature) with moisture content of 100 parts per million.

As used herein, the term challenge refers to a test colony or specimenof 10⁶ specified target pathogenic organisms.

As used herein, the term hypocompatible shall mean no significant ordebilitating degradation effects to materials and surfaces exposed tothe composition including for example, discoloration, corrosion,cracking, and embrittlement.

The specific monohydric alcohols, polyhydric alcohols, glutaraldehydeand cationic surface active agent and relative ratios complement andinteract synergistically to create the desired solubility, specificgravity, conductivity, pH, flash point, boiling point and evaporationrequired for the effective use of the cold chemical sterilant againstthe challenge as defined herein on pathogens as described herein with anontoxic effect as defined herein and with a hypocompatible effect asdefined herein on the surfaces described herein.

Further, the polyhydric alcohol reduces the harmful effects ofcomposition if swallowed or sprayed into the eyes or on mucus membranesas well as soothing the skin upon contact. Since the polyhydric alcoholreduces toxicity to human cells the need to dilute the cold sterilanthas been eliminated. Tests indicate that the polyhydric alcoholincreases the overall effectiveness of the composition against mostviruses, mold and mildew and bacterial spores.

Since the cold chemical sterilant was developed for use on a widevariety of instruments and devices the measure of chemical resistance isimportant to permit broad use and application. To be effective, the coldsterilant must be hypocompatable with CPVC, Epoxy, Polypropylene, PVC,Cyolac (ABS), Phenolic, Nylon, Noryl, Delrin (Acetal), Ryton to 200% F,Kynar, Teflon, Stainless Steel 316, Stainless Steel 304, Carpenter 20,Stainless steel (440), Titanium, Cast Bronze, Cast Iron, Aluminum,Hastelloy C, Carbon/ceramic, Ceramagnet A, Viton, Buna N., Neoprene,Nitrile, Natural rubber, Hypalon, EPDM, Kel-F, Tygon, Silicone, Ceramicand Carbon/graphite.

Comparative results of the cold chemical sterilant with the individualconstituents have demonstrated that the combination of interactiveingredients provides a cold chemical sterilant compatible with anexpansive range of materials found in a wide variety environments.

In order to accomplish the design criteria of a hypocompatiblebiodegradable nonaqueous cold chemical sterilant effective against thewide range of pathogenic target organisms described herein, thecomposition should have a pH of between about 6.0 and 7.5 or essentiallyneutral, have an effective kill time of about 8 to 12 minutes and leaveno toxic residue, a specific gravity of about 0.85, viscosity below 4and relatively no conductivity.

Standard Association of Official Analitical Chemists (A.O.A.C.) tests ofthe instant invention have been conducted against the target organismsdescribed herein including Bacillus subtilis, Clostridium sporogenes.The cold sterilant has killed the target organisms within ten minutes.

The effective proportional relationship of the ingredients by weight forthe monohydric alcohol is between about 65 percent to 75 percent, forthe polyhydric alcohol is between about 4 percent and 16 percent and forboth the saturated dialdehyde and cationic surface active agents isbetween 0.1 to 2.0 percent.

The preferred proportional relationship of the ingredients by weight isabout 70 percent for the monohydric alcohol, between about 8 to 12percent for the polyhydric alcohol, and between about 0.5 to 1.0 percentfor both the saturated dialdehyde and cationic surface active agent. Asa result there is no dermal toxicity. In addition, since there is noelectrolitic activity there is no significant positive interactionbetween the composition and the instruments.

It will thus be seen that the objects set forth above, among those madeapparent from the preceding description are efficiently attained andsince certain changes may be made in the above construction withoutdeparting from the scope of the invention, it is intended that allmatter contained in the above description or shown in the accompanyingdrawing shall be interpreted as illustrative and not in a limitingsense.

It is also to be understood that the following claims are intended tocover all of the generic and specific features of the invention hereindescribed, and all statements of the scope of the invention which, as amatter of language, might be said to fall therebetween.

Now that the invention has been described,

What is claimed is:
 1. A hypocompatible nonaqueous cold chemicalsterilant for use on medical and dental instrument devices to kill achallenge of target organisms effective against bacteria includingStaphylococcus aureus, Pseudomonas aeruginosa, Salmonella chloerasuisand spores, viruses including HIV-I, HIV-II and herples simpex 2,tuberculosis, polio and the fungus Trichophyton mentagrophytus, mold,mildew and spores, said cold chemical sterilant comprising about 65percent to about 75 percent by weight of a monohydric alcohol selectedfrom the group consisting of isopropyl, methyl, ethyl, n-propyl,n-butyl, tert-butyl and allyl and mixtures thereof, about 4 percent toabout 16 percent by weight of a polyhydric alcohol selected from thegroup consisting of propylene glycol; 1,3 propanediol; 1,2 butanediol,polyethylene glycol; glycerol and 1,4 butanediol and mixtures thereof,less than 2.0 percent by weight of a dialdehyde selected from the groupconsisting of malonaldehyde, succinaldehyde, oxaldehyde (glyoxal),adipaldehyde and glutaraldehyde and about 0.1 percent to about 2.0percent by weight of a cationic surface active agent in proportion byweight to denature the proteins to corrupt and penetrate the bacterialspore wall to kill the endospores and other microorganisms wherein thepH of said cold chemical sterilant is between about 6.0 to about 7.5 2.The hypocompatible biodegradable nonaqueous cold chemical sterilant ofclaim 1 wherein the molecular weight of polyethylene glycol is 400 orless.
 3. The hypocompatible nonaqueous cold chemical sterilant of claim1 wherein said monohydric alcohol is about 70 percent by weight, saidpolyhydric alcohol is between about 8 to about 12 percent weight, andsaid dialdehyde and said cationic surface active agent are each lessthan 1.0 percent by weight.
 4. The hypocompatible nonaqueous coldchemical sterilant of claim 1 wherein the pH of said hypocompatiblebiodegradable nonaqueous cold chemical sterilant is about 7.0.
 5. Thehypocompatible nonaqueous cold chemical sterilant of claim 1 whereinsaid dialdehyde is glutaraldehyde less than 1.0 percent by weight andsaid cationic surface active agent is cetylpyridinium chloride less than1.0 percent by weight.
 6. The hypocompatible nonaqueous cold chemicalsterilant of claim 1 wherein said monohydric alcohol is isopropylalcohol about 70 percent by weight and said polyhydric alcohol ispropylene glycol or polyethylene glycol between about 8 and about 12percent by weight.